Florfenicol, the fluoro derivative of thiamphenicol, has the structure of Formula I

Florfenicol is a broad-spectrum antibiotic compound possessing activity against many Gram negative, Gram positive, and thiamphenicol-resistant microorganisms. Florfenicol, chemically known as (1R,2S)-2-dichloroacetamido-3-fluoro-1-[4-(methylsulfonyl)phenyl]-1-propanol, is of interest as a veterinary product.
Several prior-art references have described the process of preparing Florfenicol by acylating fluoro amine compound, (1R,2S)-1-[4-(methylsulfonyl)phenyl]-2-amino-3-fluoro-1-propanol (II) with dihaloacetatic acid ester as shown below:

U.S. Pat. No. 4,235,892 describes a process of converting thiamphenicol into Florfenicol and other analogs. The process disclosed therein involves hydrolysis of thiamphenicol to produce aminodiol hydrochloride. Subsequently, amino group of aminodiol hydrochloride is protected with phthalic anhydride and fluorination is carried out to produce a phthalimido-fluoro alcohol. Thereafter, removal of the protecting group with hydrazine hydrate followed by acylation of the resulting fluoro amine compound with methyl dichloroacetate results in Florfenicol. This process does not provide Florfenicol of high purity and therefore further purification using column chromatography was carried out in the disclosed process.
U.S. Pat. No. 5,567,844 claims a process of acylation of Fluoro amine compound (II) with dihaloacetic acid in the presence of catalytic amounts of trialkylamine. However, this process is not exemplified in this reference.
Subsequently, Journal of Organic Chemistry, 55, 1990, 5291-5294, describes a commercial process for the production of Florfenicol wherein acylation of Fluoro amine compound (II) in methanol has been carried out with 5 mole equivalent of methyl dichloroacetate in presence of 1 mole equivalent of triethylamine. This acylation reaction has been accomplished by stirring for 18 hours at room temperature.
The acylation reaction of Fluoro amine compound (II) with dihaloacetic acid or with methyl dihaloacetate does not go to completion even after prolonged stirring and therefore extensive purification of Florfenicol is required to remove unreacted Fluoro amine. This results in lower yield, thereby adding on to the cost of Florfenicol.
In the instant invention, we have found that acylation of Fluoro amine compound with haloacetic acid ester can be conveniently carried out in presence of an inorganic base.